We will use stable isotopic tracers to study the effect of aerobic exercise on protein metabolism in human subjects. Our hypothesis is that exercise induces an increased rate of muscle protein breakdown and efflux nitrogen (N). This N is taken up in the liver, whereupon it is incorporated into plasma proteins (rather than urea) at an increased rate. Thus, net protein breakdown, at the whole-body level, may not be significantly affected by exercise. We will test this general hypothesis by directly measuring the rate of synthesis of specific plasma proteins before and during exercise using 13C-leucine and 15N- glycine. Plasma 13C-alpha-ketoisocaprate and urinary 15N- hippurate enrichment will be determined by gas-chromatography mass-spectrometry in order to determine the intracellular precursor enrichment for synthetic rates. Muscle protein breakdown will be assessed by changes in the rate of urinary excretion of 3-methylhistidine, and, in selected patients, muscle protein synthetic rates will be directly assessed by biopsy of muscle tissue and measurement of the rate of incorporation of 13C-leucine. We plan to investigate the response of protein metabolism during exercise under controlled conditions in which prior protein and energy intake are varied. We propose that variations in protein intake will alter the capacity of the liver to direct amino acids into plasma proteins, as opposed to urea, and that alterations in energy intake (with constant protein intake) will affect the rate of muscle protein breakdown during exercise. The results of this study will, for the first time, provide quantitative data from human subjects regarding the effect of exercise on directly-measured protein synthetic rates under controlled dietary conditions. This will be of fundamental importance in understanding the overall response to exercise, with the results having direct implications regarding the dietary requirements for optimal physical performance during periods of prolonged, aerobic work.